Colon cancer is the third most commonly diagnosed cancer and the third leading cause of cancer death in both men and women in the United States. About 30 percent of colorectal cancer (CRC) patients are at a high risk of recurrence, yet factors that determine recurrence are not fully understood. Tumor stage is currently the best prognostic marker of CRC recurrence, but we are not yet able to confidently discriminate between aggressive cancers and those not likely to recur. A need therefore exists to establish predictive markers that rapidly identify patients whose primary tumor are likely to recur, to enable tailored treatment decisions. Using a prospective cohort study of colorectal cancer patients with repeat, extensive follow-up data, we will test the hypothesis that circulating levels of specific miRNAs in colorectal cancer patients correlate with the pathophysiology of the cancer, as indicated by tumor stage, recurrence, and tumor miRNA expression levels. We expect to provide evidence that circulating miRNAs can be used as a robust non-invasive biomarker of colorectal cancer recurrence. We propose to measure by qRT-PCR the expression of miRNAs for which literature exists supporting their prognostic potential in colorectal cancer. We will evaluate whether plasma levels of these miRNAs pre-surgery, 6 months post surgery, or the change between the two, correlates with tumor stage or recurrence. We will also correlate plasma and tumor miRNA expression for a subset of patients. The rationale for the proposed research is that circulating miRNAs have shown a strong correlation with disease in CRC patients, thus we propose to determine the utility of circulating miRNA measurements both before and after surgery as biomarkers for CRC recurrence. The validation of these new biomarkers in multiple, independent study populations is a necessary step towards translating this research into clinical practice. Furthermore, correlations between pre-surgical circulating miRNA levels and tumor stage will provide evidence on the utility of these biomarkers as early detection markers. This study is innovative because it will be the first to evaluate circulating levels of miRNA both prior to and 6 months post-surgery. PUBLIC HEALTH RELEVANCE: Colorectal cancer is a leading cause of death, partly because we do not predict well which patients have cancers that are likely to recur and which do not. Our long term goal is to prevent deaths from colorectal cancer by developing and validating biomarker assays, based on miRNA molecules, that can distinguish aggressive from non-aggressive cancers. Such assays would improve outcomes by quickly identifying which patients need additional treatment or closer monitoring.